1. Field of the Invention
The present invention is in the field of automated analytical chemistry systems, and is particularly directed toward automated systems for sequentially determining the dissolution rates of a series of chemical samples.
2. Description of the Prior Art
U.S. Pat. No. 3,802,272 issued Apr. 9, 1974 to Bischoff et al for Automatic Dissolution Rate Determinator illustrates and describes the state of the art prior to the present invention. Said U.S. Pat. No. 3,802,272 discloses apparatus for automatically sequentially withdrawing samples from a series of six dissolution test chambers and pumping them through the flow cell of a detector such as an ultraviolet spectrophotometer, and returning each sample to its respective dissolution chamber. A six-way intake valve and six associated intake tubes are employed for sequentially delivering the six samples to the testing apparatus, and a separate six-way return valve and six associated return tubes are employed for sequentially returning the samples to the respective sample chambers. A peristaltic pump is required for moving the samples through the apparatus, and air pressure from a separate source is employed to purge or back-flush some of the lines through the six-way intake valve after each sample has been tested to reduce carryover or crossover with the next sample to be tested.
There are several serious problems that are inherent in such prior art apparatus which are overcome by the present invention. One such problem is that the need for two separate six-way valves and associated delivery tubes makes the apparatus undesirably complicated and expensive.
Another problem with such prior art apparatus is the requirement that a peristaltic pump be employed for flowing the samples. Peristaltic pumps have long been used in the art but have the disadvantage that the working life of the active tubing in a peristaltic pump is limited to a short period, measured in hours, and the tubing must be constantly changed. This is not only a source of annoyance and trouble to the operator, but it also makes it impossible to run extended uninterrupted dissolution tests with the automated equipment over dissolution periods that are required to have a duration longer than the life of the pump tubing. This short operational life of the peristaltic pump tubing is a critical problem with respect to some delayed release drug dissolution testing wherein the testing must be conducted over periods of several days up to several weeks, it being impossible to maintain a peristaltic pump in operation without changing the tubing for such extended periods of time. A still further problem with the use of a peristaltic pump is that tetrafluorinated hydrocarbon materials which are substantially inert to most all chemicals have not been found suitable for use in peristaltic pump tubing, and the only tubing materials available for such pumps have been plastic compositions which exhibit substantial deterioration with some dissolution media and chemicals and can be a source of interfering molecules in the detection system.
A further serious problem in connection with such prior art automatic dissolution rate testing apparatus is that in some instances the concentration of chemical in the sample might be either too strong or too weak to fall within the optimum or effective range of the detector for quantitative determination of the absorbence in a spectrophotometer, fluorescence in a fluorometer, or other type of detection. In the prior art this has required replacement of flow cells attempting to come within the detector range, or separate sample processing outside of the automated system, neither of which is a satisfactory solution to the problem.
A still further problem in connection with such prior art apparatus is that the use of a separate return valve and associated tubes makes it difficult to adequately purge the lines after each sample has been tested, and usually there will be some residual sample remaining in one or more of the lines which will result in some carryover or crossover with the next succeeding test.
A still further problem in connection with such prior art automated dissolution rate testing apparatus is that the air pressure purging part of the system tends to cause bubbling or foaming in the samples, which tends to result in inaccurate readings in the detector. This problem can be a very serious one where a high degree of accuracy is required in the result.